Switching Anti-TNF-Alpha Agents in Rheumatoid Arthritis (RA)

NCT ID: NCT00796705

Last Updated: 2012-10-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2010-10-31

Brief Summary

Rheumatoid Arthritis (RA) is a systemic inflammatory autoimmune disorder that leads to inflammation and progressive joint damage affecting 2.5 million people in the United States. The primary purpose of this study is to determine the effectiveness of switching to an alternative Tumor Necrosis Factor (TNF) alpha inhibitor in comparison to continuing treatment with an existing TNF-alpha inhibitor in adults suffering from RA in a setting of inadequate clinical response to etanercept or adalimumab.

Detailed Description

Over the past 10 years, advancements in biotechnology have revolutionized Rheumatoid Arthritis (RA) therapeutics with biologically-derived immunomodulating compounds. Tumor Necrosis Factor (TNF) alpha inhibitors constitute the largest class of these new biologic therapies. The purpose of this study is to determine the effectiveness of switching to an alternative TNF-alpha inhibitor in comparison to continuing treatment with an existing TNF-alpha inhibitor in adults suffering from RA who have had inadequate clinical response to the study drugs etanercept and adalimumab.

This study will last approximately 16 weeks. Participants will be randomized into two arms and receive injections once per week for 12 weeks. Participants in the adalimumab arm will receive alternating subcutaneous adalimumab and adalimumab placebo injections. Participants in the etanercept arm will receive subcutaneous etanercept injections.

This study consists of thirteen study visits after randomization. Study visits will occur on a weekly basis for 12 weeks prior to a follow-up visit at Week 16. A vital signs measurement and adverse event assessment will occur at each visit. A physical exam, assessment of tender and swollen joints, medication assessment, and blood collection will occur at Weeks 4, 8, 12, and 16.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Adalimumab / Adalimumab Placebo

1 sub-cutaneous (SQ) injection of adalimumab or 1 SQ injection of placebo will be given in a blinded and alternating fashion for a total of 12 weeks

Group Type: EXPERIMENTAL

Adalimumab

Intervention Type: DRUG

40 mg injection of adalimumab administered subcutaneously

Adalimumab placebo

Intervention Type: DRUG

1.0 ml .9% saline placebo administered subcutaneously

Etanercept

Participants will receive 1 SQ injection of etanercept each week for 12 weeks

Group Type: EXPERIMENTAL

Etanercept

Intervention Type: DRUG

50 mg dimeric fusion protein administered subcutaneously

Interventions

Adalimumab

40 mg injection of adalimumab administered subcutaneously

Intervention Type: DRUG

Adalimumab placebo

1.0 ml .9% saline placebo administered subcutaneously

Intervention Type: DRUG

Etanercept

50 mg dimeric fusion protein administered subcutaneously

Intervention Type: DRUG

Other Intervention Names

Humira; Humira placebo; Enbrel

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Rheumatoid Arthritis
• Current treatment with either etanercept or adalimumab for at least 12 weeks prior to randomization
• Disease Activity Score (DAS) C-reactive Protein (CRP) 28 ≥ 4.4
• Treatment with concomitant Disease-Modifying Anti-Rheumatic Drugs (DMARDs) is permitted but not required as described below:

1. Methotrexate - maximum dose of 25 mg per os (PO), intra-muscular (IM), or SQ weekly.

2. Leflunomide - maximum dose of 20 mg PO daily.

3. Sulfasalazine - maximum dose of 1,500 mg PO twice daily.

4. Hydroxychloroquine - maximum dose of 400 mg PO daily.

• If taking DMARD(s), subjects must be on stable doses for at least 12 weeks prior to randomization.
• If treated with prednisone (or equivalent corticosteroid), on a stable dose of <= 10 mg/day for 28 days prior to randomization.
• Agree to use appropriate form of contraception. More information on this criterion can be found in the protocol.

• Concurrent use of any biologic agent other than etanercept or adalimumab
• Concomitant immunosuppressive therapy other than the Disease-Modifying Anti-Rheumatic Drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), or corticosteroids specified in the protocol
• Presence of open leg ulcers
• Chronic or persistent infection that may be worsened by immunosuppressive treatment. More information on this criterion can be found in the protocol.
• Active infection or severe infections requiring hospitalization or treatment with intravenous antibiotics, antivirals, or antifungals within 30 days prior to randomization
• History of positive Purified Protein Derivative (PPD) or chest x-ray findings indicative of prior tuberculosis infection
• Any medical condition or treatment that, in the opinion of the investigator, would put the subject at risk by participation in the study
• History of malignancy. More information on this criterion can be found in the protocol.
• Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
• Investigational biological or chemical agents within 4 weeks prior to randomization.
• History of drug or alcohol abuse within a year prior to randomization
• Treatment with natalizumab, rituximab, or another B-cell depleting therapy within a year prior to randomization
• Treatment with infliximab, abatacept, tocilizumab, golimumab, or certolizumab pegol within 12 weeks prior to randomization.
• Known allergy or hypersensitivity to study products
• Any psychiatric disorder that prevents the participant from providing informed consent
• Inability to follow protocol instructions
• Pregnant or breastfeeding

Exclusion Criteria

• Diagnosis of another autoimmune disease likely to require immunosuppression. More information on this criterion can be found in the protocol.
• Failing treatment with etanercept if previously treated with adalimumab
• Failing treatment with adalimumab if previously treated with etanercept
• Intraarticular injection within 4 weeks prior to randomization

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Larry Moreland, MD

Role: STUDY_CHAIR

University of Pittsburgh

Mark Genovese, MD

Role: STUDY_CHAIR

Stanford University

Locations

University of Alabama

Birmingham, Alabama, United States

Stanford University

Palo Alto, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Sarasota Arthritis Research Center

Sarasota, Florida, United States

Tampa Medical Group

Tampa, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Justus Fiechtner, MD, PC

Lansing, Michigan, United States

Feinstein Institute for Medical Research NS-LIJ

Manhassett, New York, United States

University of Rochester

Rochester, New York, United States

Carolina Bone and Joint

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Baylor Research Institute

Dallas, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

Villeneuve E, Haraoui B. To switch or to change class-the biologic dilemma in rheumatoid arthritis. Nat Rev Rheumatol. 2010 May;6(5):301-5. doi: 10.1038/nrrheum.2010.45. Epub 2010 Apr 13.

Reference Type: BACKGROUND

PMID: 20386564 (View on PubMed)

Rubbert-Roth A, Finckh A. Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Arthritis Res Ther. 2009;11 Suppl 1(Suppl 1):S1. doi: 10.1186/ar2666. Epub 2009 Apr 6.

Reference Type: BACKGROUND

PMID: 19368701 (View on PubMed)

van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998 Oct;41(10):1845-50. doi: 10.1002/1529-0131(199810)41:103.0.CO;2-K.

Reference Type: BACKGROUND

PMID: 9778226 (View on PubMed)

Other Identifiers

DAIT ARA05

Identifier Type: -

Identifier Source: org_study_id